COX15

PF3D7_1435000 (COX15) has been experimentally implicated only as a component physically associated with the mitochondrial electron-transport machinery in Plasmodium falciparum. In a chemoproteomic target-profiling study, a photoactivatable derivative of 9-methoxystrobilurin G enriched COX15 together with QCR7 and QCR9, placing COX15 at or near the inhibitor's binding site within the complex III functional unit; resistance mutations mapping independently to cytochrome b reinforced this complex III association (PMID:39262389). Beyond this enrichment-based assignment (PMID:39262389), no direct enzymatic activity, substrate, structural model, or dedicated functional characterization of COX15 itself has been established in the available corpus.

1. 2024 Low

   To identify the molecular targets of the antimalarial strobilurin 9-methoxystrobilurin G, chemoproteomic profiling asked which parasite proteins sit at the inhibitor binding site — and this placed COX15 within the mitochondrial complex III functional unit.

   Evidence Chemical pulldown/enrichment with a photoactivatable 9MG derivative, plus genome sequencing of drug-resistant clones and a ubiquinone cytochrome c reductase activity assay, in P. falciparum 3D7 and Dd2

   PMID:39262389

   Open questions at the time

   • Single chemoproteomic pulldown from one lab; COX15 enrichment indicates proximity/association but was not independently confirmed
   • No direct enzymatic activity, substrate, or catalytic role for COX15 itself was demonstrated
   • Resistance mutations mapped to cytochrome b, not to COX15, leaving COX15's specific contribution to the complex undefined

• Whether COX15 has an intrinsic enzymatic or assembly function, its structure, and its specific role within the mitochondrial electron-transport complex remain uncharacterized.
• No structural model or defined molecular activity for COX15
• No genetic knockout/knockdown phenotype establishing its cellular role
• Its precise position and function within the complex III functional unit are undefined